In lung cancer arachidonic acid (AA) is metabolized by COX leading to prostaglandin (PG) production. In non-small cell lung cancer (NSCLC) PGE2 is a major product. NSCLC PGE2 levels and proliferation are inhibited by non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin. Proliferation and PGE2 levels are increased by epidermal growth factor (EGF). In particular, EGF increases COX-2 mRNA in NSCLC cell lines NCI-H157, H1264 and H1299.In the present period receptor binding studies were conducted. 3H-PGE2 bound with high affinity to membranes derived from NSCLC cell line NCI-1299. 3H-PGE2 binding was inhibited with high affinity by PGE2 and PGE1 but not PGD2. Also 3H- PGE2 binding was inhibited by GTP, suggesting that the EP2 receptor interacts with a G-protein. PGE2 elevated cAMP and increased c-fos mRNA but had no effect on cytosolic Ca2+. The effects of PGE2 on cAMP were antagonized by AH6809. AH6809 inhibited the proliferation of NSCLC cells. These results indicate the biologically active PG receptors are present on NSCLC cells.PGE2 increase vascular endothelial cell growth factor (VEGF) mRNA in lung cancer cells. Both SCLC and NSCLC cells had high levels of VEGF, an angiogenic factor. By ELISA, VEGF was secreted into conditioned media exposed to NSCLC cells. By RT-PCR the major forms of VEGF synthesized in NSCLC cells were VEGF121, VEGF165 and VEGF180. The increase in VEGF mRNA caused by PGE2 was inhibited by somatostatin, which decreases cAMP levels, and H89, a protein kinase A inhibitor. These results suggest that PGE2 may be an important mediator between growth factors, which stimulate tumor proliferation, and angiogenic factors which increase tumor vasculature. - COX-2, PGE2, VEGF, lung cancer, - Human Tissues, Fluids, Cells, etc.